Tricyclic imines

ABSTRACT

Tricyclic imines of the formula   WHEREIN R1, R2, R3, R4, X, m and n are as hereinafter described, PREPARED FROM THE CORRESPONDING KETONES OF THE FORMULA   WHREIN R1, X and m are as hereinafter described, are disclosed. The compounds of formula I are useful as antidepressants, as well as anticonvulsants and agents for the treatmment of Parkinsonism.

United States Patent [1 1 Dostert et al.

[ May6, 1975 TRICYCLIC [MINES [75] Inventors: Philippe Dostert, Basel;Emilio Kyburz, Reinach. both of Switzerland [73] Assignee: Hoffmann-LaRoche Inc., Nutley,

[22] Filed: Jan. 14, I974 21 Appl. No.1 433,319

Related US. Application Data [62] Division of Ser. No. l84,90l, Sept.29, l97l. Pat.

[30] Foreign Application Priority Data Oct. 9 I970 Switzerland [4972/70[52] US. Cl 260/456 A [5 l] Int. Cl C07c 143/68 [58] Field of Search260/456 A. 465 E, 47l A, 260/327 B, 333, 566 R [56] References CitedUNITED STATES PATENTS 3,257,404 6/1966 Fouche 260/456 A 3,526,671 9/l970Judd 260/456 A Primary Examiner-Bernard Helfin Assistant Examiner-NickyChan Attorney, Agent, or FirmSamuel L. Welt; Bernard 5. Leon; William G.lsgro [57] ABSTRACT Tricyclic imines of the formula wherein R R R R X mand n are as hereinafter described,

prepared from the corresponding ketones of the formula 1 (R m H whrein RX and m are as hereinafter described, are disclosed. The compounds offormula I are useful as antidepressants, as well as anticonvulsants andagents for the treatmment of Parkinsonism.

2 Claims, No Drawings TRICYCLIC IMINES This is a division of applicationSer. No. 184,901, filed Sept. 29, 1971, now US. Pat. No. 3,803,234.

wherein X is sulfur, oxymethylene, thiomethylene,

ethylene, lower alkanoylamido substituted ethylene, vinylene or vinylenesubstituted by halogen, lower alkyl, cyano or sulfamoyl; R is hydrogen,halogen, hydroxy, lower alkoxy, lower alkyl, cyano, loweralkoxycarbonyl, carbamoyl, sulfamoyl, lower alkylmercapto,trifluoromethyl or nitro; R and R individually, are hydrogen or loweralkyl, or R and R together with the nitrogen atom, are a monocyclic,saturated 5- or 6-membered heterocyclic group which may contain anoxygen or sulfur atom or an additional nitrogen atom; R is hydrogen orlower alkyl; m is an integer from 1 to 3; and n is an integer from 2 to5,

and the pharmaceutically acceptable acid addition salts thereof. Thecompounds of formula I are useful as antidepressants, as well asanticonvulsants and as agents for the treatment of Parkinsonism.

In another aspect, the invention relates to intermediates of the formulawherein R is cyano or lower alkoxycarbonyl. In yet another aspect, theinvention relates to intermediates of the formula wherein R, R, X, m andn are as previously described and Y is halogen, lower alkylsulfonyloxy,phenylsulfonyloxy, or phenylsulfonyloxy substituted by lower alkyl orhalogen.

DETAILED DESCRIPTION OF THE INVENTION The invention relates to compoundsof the formula X l (Rllm N 2 I IH) 41 l n R R4 wherein X is sulfur,oxymethylene, thiome thylene,

ethylene, lower alkanoylamido substituted ethylene, vinylene or vinylenesubstituted by halogen, lower alkyl, cyano or sulfamoyl; R is hydrogen,halogen, hydroxy, lower alkoxy, lower alkyl, cyano, loweralkoxycarbonyl, carbamoyl, sulfamoyl, lower alkylmercapto,trifluoromethyl or nitro; R and R individually, are hydrogen or loweralkyl, or R and R together with the nitrogen atom, are a monocyclic,saturated 5- or 6-membered heterocyclic group which may contain anoxygen or sulfur atom or an additional nitrogen atom; R is hydrogen orlower alkyl; m is an integer from I to 3; and n is an integer from 2 to5, and the pharmaceutically acceptable acid addition salts thereof.

As used herein, the term lower alkyl denotes a straight or branchedchain saturated hydrocarbon group containing from l-6 carbon atoms, forexample, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, neopentyl,pentyl, hexyl, and the like. The term lower alkoxy" denotes an alkylether group in which the lower alkyl group is as described above, forexample, methoxy, ethoxy, propoxy, pentoxy, and the like. The termhalogen denotes all the halogens, i.e., bromine, chlorine, fluorine andiodine; of these, fluorine, chlorine and bromine are preferred. The termlower alkanoylamido denotes a radical wherein the alkanoyl group isderived from an aliphatic carboxylic acid, e. g., an alkanecarboxylicacid, of 1-6 carbon atoms, for example, formyl, acetyl, propionyl, andthe like. The carbamoyl and sulfamoyl groups can be optionally monoordi-substituted by lower alkyl, for example, monomethyl ordi-methylaminocarbonyl, mono-methyl or diethylaminosulfonyl, and thelike. The monocyclic, saturated 5- or 6-membered heterocyclic groupsformed by R and R and the nitrogen atom to which they are attached canbe pyrrolidino, piperidino, piperazino, morpholino, thiamorpholino, andthe like, as well as the corresponding groups which are substituted bylower alkyl, lower alkoxyalkyl, amino or lower alkylamino.

A preferred subgenus of the tricyclic imines of the invention comprisescompounds of the formula I R Ia.

wherein X, R, R R R and n are as previously described, and thepharmaceutically acceptable acid addition salts thereof.

A particularly preferred subgenus of the tricyclic imines of theinvention comprises the compounds of formula la, wherein X is ethyleneor vinylene, R is hydrogen or halogen, R and R individually, arehydrogen or lower alkyl, R is hydrogen and n is 2 or 3.

The most preferred tricyclic imines of the invention are:

3-chloro-N-{ 2-dimethylamino-ethyl)- l 0,1 l-dihydro5H-dibenzo{a,d}cyclohepten-5-imine;l-chloro-N-(2-dimethylamino-ethyl)-10,1 l-dihydro-5H-dibenzo[a,d]cyclohepten-5-imine;

N-( 2-dimethylamino-ethyl)- l 0,1 l-dihydro-SH-dibenzo[a,d]cyclohepten-5-imine; andl-bromo-N-(2-dimethylamino-ethyl)10,] l-dihydro-5H-dibenzo[a,d]cyclohepten-5-imine.

Exemplary of the compounds of formula I are:

N-(3-ethylamino-propyl)-10,1 l-dihydro-S H-dibenzo-la,d]cyclohepten-5-imine;

N-(2-dimethylamino-ethyl)-10,ll-dihydro-Sl-ldibenzo[a,d]cyclohepten-S-imine;

clohepten-S-imine;

clohepten-S-irnine; 3-ch]oro-N-(2-dimethylamino-ethyl)-10,1 l-dihydro-5H-dibenzo[a,d]cyclohepten-5-imine; 1-chloro-N-( 2 dimethylamino-ethyl10,1 l-dihydro- 5H-dibenzo[a,d]cyclohepten-5-imine;

l -bromo-N-(2-dimethylamino-ethyl)- 10,1 l-dihydro-5H-dibenzo[a,d]cyclohepten-5-imine;

l -methyl-N-(3-diethylamino-propyl)- 10,1 l-dihydro-5H-dibenzo[a,d]cyclohepten-5-imine;l-cyano-N-(2-dimethylamino-ethyl)-10,1 l-dihydro-5H-dibenzo[a,dlcyclohepten-S-imine;

I-br0mo-N-( Z-dimethylamino-ethyl H- dibenz0[a,d]cyclohepten-5-imine;

2-chloro-N-( S-diethylamino-propyl )thioxanthen-9- imine; l0-cyano-N-(Z-dimethylamino-ethyl )-5 H- dibenzo[a,d]cyclohepten-5-imine;lO-acetamidoN-(Z-dimethylamino-ethyl)-5H-dibenzo[a,d]cyclohepten-5-imine; 3-chloro-N(2-morpholino-ethyl)- 10, ll-dihydro-Sl-ldibenzo[a,d]cyclohepten-5-imine; 3-chloro-N-[2-(4-methyl-piperazino )-ethyl 10,1 ldihydro-5H-dibenzo[a,d]cyclohepten-5-imine;

l'chloro-N-( 'l-dimethylaminol methylethyl 10,1 l-dihydro-SH-dibenzo[a,d lcyclohepten-S- imine;

4 l-chloro-N-(2-amino-ethyl)-10,1 I dihydro-SH-dibenz0[a,d]cyc|ohepten-5-imine; and the like. The compounds of formulaI and their pharmaceuti cally acceptable acid addition salts can beprepared by 5 reacting a ketone of the formula 1 (R m 1 II wherein X, Rand m are as previously described,

with a diamine of the formula R H2- (CH) N 3 III R 4 wherein R R, R andn are as previously described, or by reacting a compound of the formulam IV CH Y (1 4 wherein X, R, R, m and n are as previously described andY is halogen, lower alkylsulfonyloxy, phenylsulfonyloxy orphenylsulfonyloxy substituted by lower alkyl or halogen,

with an amine of the formula wherein R and R are as previouslydescribed, and, if desired, converting a compound of formula I soobtained into a pharmaceutically acceptable acid addition salt.

According to one process embodiment of the invention, the compounds offormula I are prepared by reacting a ketone of formula II with a diamineof formula II].

The ketone starting materials of formula ll are, in general, known. Anovel ketone starting material of formula ll is 3-cyanolO,ll-dihydro-5H-dibenzo[a,dlcyclohepten-S-one, which can be prepared in aknown manner, for example. by treating the corresponding ketone which issubstituted in the 3-position by a halogen atom, preferably by a bromineatom, with a cyanide,

preferably, copper cyanide, conveniently in a solvent such as, forexample, dimethylformamide and the like. The 3 (loweralkoxycarbonyl)-l0,l l-dihydro-SH- dibenzola,d]cyclohepten-5one startingmaterials of formula II, for example, 3-methoxycarbonyl-l0,lldihydro-5H-dibenzo[a,d]cyclohepten-5-one, are also novel. They can beprepared from the corresponding ketone, which is substituted in the3-position by a cyano group, by saponification in a known manner andesterification of the resulting ketone which is substituted in the3-position by a carboxyl group. The novel ketone starting materials offormula [I hereinbefore also form part of the present invention.

The diamine starting materials of formula III are known compounds.

The reaction ofa ketone of formula ll with a diamine of formula III canbe carried out by heating. Preferably, they are heated together at atemperature at which no decomposition occurs; that is, at a temperaturein the range of between about 50 and about 250C. It is advisable tocarry out this thermal reaction under an atmosphere of an inert gas,such as, nitrogen, argon or the like.

A ketone of formula ll can, however, also be reacted with a diamine offormula III with the aid of a neutral or acidic dehydrating agent.Preferred neutral dehydrating agents are the so-called molecular sieveswhich are ion-exchangers having wide internal pores accessible onlythrough relatively narrow channels; for example, synthetic zeolite,sodium aluminum silicate, calcium aluminum silicate and the like. As theacidic dehydrating agent, generally, there can be used Lewis acids,preferably the halides of an element from Group III, IV, V or VII] ofthe Periodic System. Examples of such Lewis acids are, from Group III,boron trifluoride and aluminum trichloride, from Group IV titaniumtetrachloride and germanium tetrachloride, and from Group V arsenictrichloride, antimony trichloride and antimony pentachloride. Of theseLewis acids, titanium tetrachloride and antimony trichloride arepreferred.

When a ketone of formula II is reacted with a diamine of formula IIIwith the aid of a neutral dehydrating agent, there is advantageouslyused one of the aforementioned ion-exchangers having a pore diameter ofabout 4A and a granular size of about 2 mm. This reaction isconveniently carried out by heating a mixture of the reactants togetherwith the chosen ionexchanger, acting as the molecular sieve, expedientlywith the addition of a solvent, preferably a hydrocarbon such as benzeneor toluene, at a temperature in the range of between about roomtemperature and the boiling point of the reaction mixture.

The reaction ofa ketone of formula II with a diamine of formula III withthe aid of one of the aforementioned Lewis acids is conveniently carriedout by allowing the reactants to react with the chosen Lewis acid at atemperature in the range of between about room temperature and theboiling point of the reaction mixture in the presence of a solvent. Ithas proven advantageous to carry out this reaction under an atmosphereof an inert gas, for example, under nitrogen, argon, or the like.

In the foregoing reaction, the choice of the solvent is dependent on thesolubility of the reactants. Suitable solvents are, for example, cyclichydrocarbons such as cyclohexane, benzene, toluene, mesitylene or thelike,

and chlorinated hydrocarbons, preferably, methylene chloride. Undercertain circumstances, the diamine of formula [ll can itself serve asthe solvent. Similarly, the Lewis acid used as the acidic dehydratingagent is conveniently utilized in solution. The solvent used for theketone can expediently be utilized as the solvent for the Lewis acid.When titanium tetrachloride, for example, is used as the acidicdehydrating agent, benzene or toluene is preferably used as the solvent.

The oxide of the dehydrating agent which is formed in the reaction isremoved by decantation or filtration. It can, if desired, be convertedto the corresponding halide which can again be employed as thedehydrating agent. The filtrate is concentrated. The concentrate isdiluted with water and extracted with a solvent suitable for theextraction of the compound of formula I, of which ether is particularlypreferred. The compound of formula I which is isolated from the extract,generally an oil, crystallizes after a short time.

According to the second embodiment of the process of the invention, thecompounds of formula I are prepared by reacting a compound of formula IVwith an amine of formula V.

The compounds of formula IV are novel and form part of this invention.They can be prepared, for example, by condensing the correspondingtricyclic ketone, which may be ring-substituted, for example, l0,lldihydro-SH-dibenzo[a,d]cyclohepten-S-one, with an amine correspondingto the sidechains that are to be introduced, for example, ethanolamine,in a known manner, expediently at an elevated temperature. In the caseof the specific examples just mentioned, halogenating, mesylating ortosylating the resulting N-(2- hydroxy-ethyl)- l 0,1l-dihydro-5H-dibenzo[a,d]cyclohepten-S-imine in a known manner, forexample, using p-toluenesulfonyl chloride conveniently in an organicsolvent, for example, a hydrocarbon such as benzene or the like, at roomtemperature.

The amines of formula V are known compounds.

The reaction of a compound of formula IV with an amine of formula V canbe readily carried out. Thus, the reaction can be carried out, ifdesired, in the presence of an acid-binding agent, for example,potassium carbonate, sodium carbonate or the like, conveniently in anorganic solvent, for example, a lower alkanol such as ethanol or thelike, or a cyclic hydrocarbon such as toluene, xylene or the like, at atemperature in the range of between room temperature and the boilingpoint of the reaction mixture.

The compounds of formula I readily form acid addition salts by treatmentwith acids, for example, with hydrohalic acids such as hydrochloricacid, hydrobromic acid and the like, with other mineral acids such assulfuric acid and the like. Treatment with one equivalent of acidsyields mono-salts, with two equivalents of acid di-salts are formed.Treatment with organic acids, such as benzoic acid, acetic acid, oxalicacid, citric acid, lactic acid, maleic acid and the like usually yieldsmonosalts. The oxalates crystallize particularly well.

Ring-substituted compounds of formula I are obtained as mixtures of thetwo stereoisomers. If desired. the stereoisomeric forms can beseparated, for example, by fractional crystallization or bychromatography A preferred embodiment of the foregoing process comprisesreacting a ketone of the formula wherein X and R are as hereinbeforedescribed, with a diamine of formula III with the aid of a Lewis acid,optionally in the presence of a solvent, and, if desired, converting thecompound of formula I obtained into an acid addition salt. A preferredaspect of this embodiment comprises using a ketone of formula Ila inwhich X is ethylene or vinylene and R is hydrogen or halogen and adiamine of formula III wherein R and R individually, are hydrogen orlower alkyl, R is hydrogen and n is 2 or 3.

The compounds of formula I and their pharmaceutically acceptable acidaddition salts are pharmacodynamically active. In particular, theypossess neuropsychotropic properties. Most of the compounds of formula lexhibit antidepressant activity, as well as anticonvulsant andanti-Parkinson activity and are therefore useful as antidepressants aswell as anticonvulsants and antiParkinson agents, in the treatment ofdepression, convulsions and Parkinsonism. Some compounds of formula Ipossess antitussive and diuretic properties, and are therefore useful asantitussive agents and diuretics. Most interesting of the compounds offormula I are:

l -chloro-N-( 2-dimethylamino-ethyl l 0, l l-dihydro-SH-dibenzo-[a,d]cyclohepten-'imine, which acts principally as anantidepressant and has very weak anticholinergic activity;N-(2-dimethylamino-ethyl)-l0,lldihydro-5H-dibenzo[a,d]cyclohepten-5-imine, which has strong centraland peripheral anticholinergic activity and3-chloro-N-(Z-dimethylamino-ethyl)-10,1 1-dihydro-5H-dibenzo[a,d]cyclohepten-S-imine, which has strongantidepressant and anticholinergic activity, the last-mentionedcompounds are very active against Parkinsonism',l-Bromo-N(2-dimethylaminoethyl)- l0,1l-dihydro-5H-dibenzo[a,d]cyclohepten-5-imine which possesses stronganticonvulsant properties; 3- chloro-N-(2-diethylamino-ethyl)-10,1l-dihydro-SI-I- dibenzo(a,dlcyclohepten-S-imine, which has strongantitussive activity; and l-chloro-( 2-diethylamino-ethyl)- l0,l l-dihydro-SH-dibenzo[a,d]cyclohepten5-imine, which has strong diureticactivity.

The toxicity of the compounds of formula I is very low, for example,l-chloro-N-(2-dimethylaminoethyl 1 0,1l-dihydro-5H-dibenzo[a,dlcyclohepten-S- imine and l-bromo-N-(2-dimethylaminoethyl)-l(),l dihydro-S l-I-dibenzo[ a,d]cyclohepten-5-imine have demonstrated an LD of about 750 mg/kg. in miceon oral administration. In rats, anticonvulsant activity is evident at adosage of 30 mg. p.o./kg.

Compounds of formula I in which X is an ethylene or vinylene group and Ris hydrogen or halogen are preferred compounds of the invention.

The compounds of formula I and their pharmaceutically acceptable acidaddition salts can be used for the treatment of illnesses of differentetiology. They can be used in the form of pharmaceutical preparationswhich contain them in association with a compatible pharma ceuticalcarrier. The carrier can be an organic or inorganic inert carrier whichis suitable for enteral or parenteral administration such as, forexample, water,

gelatin, gum arabic, lactose, starches, vegetable oils, polyalkyleneglycols, and the like. The pharmaceutical preparations can be made up insolid form, for example, tablets, dragees, suppositories or capsules, orin liquid form, for example, solutions, suspensions or emulsions. Thepreparations can be sterilized and/or can contain adjuvants such aspreserving, stabilizing, wetting or emulsifying agents or salts forvarying the 0S motic pressure. They can also contain yet othertherapeutically active substances.

The amount of a compound of formula I administered to warm-bloodedanimals varies within a wide range according to the individual compoundand to the specific needs of the warm-blooded animal being treated.However, in general, the daily dose for oral administration comprisesfrom about 50 mg. to about 200 mg. of a compound of formula I.

The following examples further illustrate the inven tion. All parts areby weight and all temperatures are in degrees Centigrade, unlessotherwise mentioned.

EXAMPLE 1 Preparation of 3-chloro-N-( 2-dimethylamin0-ethyl l 0,1l-dihydro- 5H-dibenzo[a,d lcyclohepten-Sdmine oxalate l2.l g. of3-chloro-l0,l l-dihydro-5H-dibenzo[a,d- ]cyclohepten-5-one are dissolvedin 300 ml. of absolute benzene at room temperature under an atmosphereof argon with stirring. Following the addition of 44 g. ofN,N-dimethylamino-ethylamine, the solution is cooled to 0C. and treateddropwise with a solution containing 3.6 g. of titanium tetrachloride in40 ml. of absolute benzene. The reaction mixture is stirred at roomtemperature for 48 hours and then filtered. The filtrate is concentratedunder reduced pressure. The concentrate is treated with ice and 3Nhydrochloric acid. The unreacted ketone is taken up in ether.Thereafter, the aqueous phase is made alkaline and extracted with ether.The ether extract is washed with a saturated aqueous sodium chloridesolution, dried over sodium sulfate and evaporated. The3-chloro-N-(2-dimethylaminoethyl)- lO,ll-dihydro-5H-dibenzo[a,d]cyclohepten-5-imine which is obtained is takenup in acetone and treated with a solution containing 2.8 g. of oxalicacid in 40 ml. of ethanol. The oxalate which precipitates in crystallineform melts at 200202C. after recrystallization from acetone/methanol.

The 3-chloro N( 2-dimethylamino-ethyl)- l 0, lldihydro-SH-dibenzo[a,d]cyclohepten-5-imine oxalate is obtained as astereoisomeric mixture in the ratio of about 3:1. The two isomers can beseparated by thin layer chromatography [adsorbentz aluminum oxide MerckF 254, eluting agent: acetone/toluene/diethylamine (491492)].

In an analogous manner, utilizing the procedure of Example I:

from 3-chloro-10,l l -dihydro-5l-l-dibenzo[ a,d]cycloheptenS-one andN,N-diethylamino-ethylamine, there is obtained3-chloro-N-(Z-diethylaminoethyl)-l0,l l-dihydro-5H-dibenzo[a,dlcyclohepten-S-imine, melting point 92C. (oxalate);

from 3-chlorol 0,1 ldihydro-5H-dibenzo[a,d]cyclohepten-S-one andN,N-dimethylarninopropylamine, there is obtained 3-chloro-N-(3-dimethylamino-propyU-10,] l-dihydro-SH- dibenzola,d]cyclohepten5-imine,melting point IMP-182C. (oxalate);

from 3-chlorol 0,1 l-dihydro5H-dibenzo{a,d]cyclohepten-S-one andN,N-diethylaminoethylamine, there is obtained 3chloro-N-(2dimethylamino-ethyl l 0,1 l-dihydrofil-ldibenzola,dlcyclohepten5-imine(main isomer of the mixture). melting point 2i2214C. (hydrochloride);

from 1 Oacetamido- 10,1 1 -dihydro-H-dibenzol a,d- ]cyclohepten-5-oneand N.Ndimethylaminoethylamine, there is obtained -aeetamido-N(2-dimcthylamino-ethyl l0.l ldihy(lro 5H- dibenzola.d]cyclohepten-5-imincmelting point at ca. 150C (dihydrochloride J;

from 3-chloro-10,l l-dihydro 5H-dihenzo[ a,d]cy clohepten-S-one andN-morpholino-ethylamine, there is obtained 3-ehloro-N-(2-morpholinoethyl10.1 l-dihydro-5H-dibenzo[a,d]cyclohept-- en-S-imine. melting pointl84187C. (dihydrochloride);

from 10.1 l-dihydro-l-methoxy-5H-dibenzo[a.dlcyclohepten-S-one andN,N-dimethylaminoethylamine. there is obtained 10 11-dihydro-N-(-dimethylamino-ethyl l -methoxy5H- dihenzola,dlcyclohepten-S-imine.melting point at ca. 100C. (oxalate);

from Z-chloro- 10.1 l-dihydro-5H-dibenzo[ a,d ]cyclohepten-S-one andN,N-dimethylaminoethylamine, there is obtained 2-chloro-N-(2dirnethylamino-ethyl)10 l 1-dihydro-5H- dibenzo[a.dlcyelohepten-S-imine.melting point 109-l 12C. (oxalate);

from 1 -fluoro- 10,1 l-dihydro5H-dibenzola,d )cyelohepten-5-one andN,N-dimethylaminoethylamine. there is obtained l-fluoro-N-(Z-dimethylamino-ethyl)-10,1 l-dihydro-SH- dibenzola,d)cyclohepten-S-imine,melting point 185-l88C (oxalate);

from 3-chloro- 10,1 l-dihydro-5H-dibenzo[ a,d ]cyclohepten-S-one andN,N-dimethylaminopropylamine there is obtained 3chloro-N(3-dimethylamino-propyl)-10.11dihydro5H- dibenzo[a,d]cyeiohepten-5-imine(main isomer of the mixture). melting point 274277C. (dihydrochloride);

from 3-chloro-10.1 1-dihydro-5H-dibenzo[a,d]cy

clohepten-5-one and N-(4-methylpiperazino)- ethylamine, there isobtained 3-chloro-N-[2-(4- methylpiperazino)-ethyl]-10,] l-dihydro-5H-dibenzola.dlcycloheptcn-S-imine. melting point 24o248C (dioxolate);

from 3-bromo-l0,l l-dihydro-5H-dibcnzo[a,d lcyeloheptcn-S-one andN,N-dimethylaminoethylamine. there is obtained 3-bromo-N-(2dimethylamino-ethyl)-10,l l-dihydro5H- dibenzola.d]cyclohepten-5-imine,melting point Zl5-2 l 8C. (hydrochloride);

from 3-bromol 0,1 l-dihydro-5H-dibenzo[a.d lcy ciohepten-5-one andN.N-dimethylaminoethylamine, there is obtained 3-bromo-N-(2-dimethylamino-ethyl)-10,1l dihydro-5H- dibenzola.djcyclohepten-5-imine(main isomer of the mixture), melting point WIT-183C. (dihydro'chloride);

from B-methoxywarbonyk10. 1 ldihydro-SH- dibenzol a.d lcyclohepten-S-oneand N,N- dimethylamino-ethylamine. there is obtained 3-methoxycarbonyl-Ni 2-dimethylamino-ethyl 10.1l-dihydro-5H-dibenzo[a.d]cyclohepten-5- imine, melting point lo1l64C.(oxalate);

from dibenzo[b,e lthiepin-l 1(6H )-one and N,N-dimethylaminoethylamine.there is obtained N-( 2-dimethylamino-ethyl )-dibenzo[ b,e lthiepin-1l(6H)-imine. melting point l79-182C., (oxalate);

from 1,3-dichloro- 10,1 l-dihydro-5H-dibenzo[a,d- )cyclohepten-S-onc andN.N-dimethylaminoethylamine. there is obtained 1.3-diehloro-N-(2-dimethylamino-ethyl )10,l l-dihydro-SH- dibenzola,d}cyclohepten-5-imine(trans isomer), melting point 2092l l 'Cv (dihydrochloride);

from 1,3-dichlorol 0,1 1 -dihydro-5 H-dibenzo{a,d- ]cyclohepten-5-oneand N.N-dimethylaminoethylamine, there is obtained 1,3-dichloro-N-(Ldimethylamino-ethyl)- 10,1 l-dihydro-5H- dibenzo[a.dlcycloheptemS-imine.melting point 1-44"-147"C- (hydrochloride);

from lch10ro-10 11-dihydro-7,8-dimethyl-5H- dibenzo[a,d1cyelohepten5-one and N,N- dimethylamino-ethylamine, there is obtained 1-chloro-7.8-dimethyl-N-( Z-dimethylamino-ethyl 10,11-dihydro-5H-dibenzo[a,d }cyclohepten5- imine, melting point 243-246C.(hydrochloride);

from 3cyano- 10.1 l-dihydro-5H-dibenzo[a.d ]cycloheptemS-one andN,N-dimethylaminoethylamine, there is obtained 3-cyano-N-(2-dimethylamino-ethyl)-10,1 l-dihydro-5H- dibenzo[a,dlcycloheptemiimine;melting point 242244C (hydrochloride).

clohepten-S-one and N,N-dimethylamin0- ethylamine, there is obtainedl0(or 11)-bromo-lchloro-N-(2-dimethylamino-ethyl)-5H-dibenzo[a.d]cyclohepten-5-imine. melting point 19l-193C. (oxalate); and

from 1.10(or 1 1 )-dichloro-SH-dibenzo[a,d]cyclohepten-S-one andN.N-dimethylaminoethylamine, there is obtained l,10(or l l )-dichlor0-N-(Z-dimethylaminoethyl)-5H-dibenzo[a,d]cyclohepten-S-imine. meltingpoint 183185C. (oxalate).

The 3-methoxycarbonyl-10,l l-dihydro-SH- dibenzo[a,d]eyclohepten-5-onestarting material mentioned hereinbefore can be prepared, for example,as follows:

4.6 g. of 3-cyano-10,l1-dihydro-5H-dibenz0[a,dlcyclohepten-S-one,together with 4.5 g. of potassium hydroxide, 15 ml. of ethylene glycoland 5 ml. of water are heated to boiling under reflux conditions for 48hours. The resulting solution is cooled diluted with water and extractedwith ether. The aqueous phase is adjusted to a pH 1 by addition of 3Nhydrochloric acid and extracted with chloroform. The chloroform extractis dried over sodium sulfate and evaporated. The residual 3-carboxy-10,ll dihydro-5H-dibenzo[a,d]cyclohepten-S-one melts at 22l223C.

8.8 g. of 3-carboxy-10,l1-dihydro-5H-dibenzo[a,d lcyclohepten-S-one.together with 1 10 ml. of methanol and 600 ml. of absolute benzene, areheated in a Soxhlet apparatus filled with a molecular sieve (porediameter 4A) for 12 hours. The resulting mixture is evaporated and theresidue is taken up in ether. The extract is washed with 3N sodiumhydroxide solution, dried over sodium sulfate and evaporated. Theresidual 3- methoxycarbonyll 0,1 l-dihydro-5H-dibenzo[a,d1Cyclohepten-S-one melts at 109l11C.

The 3-cyano- 1 0,1 l-dihydro-H-dibenzo[a,d]cyclohepten-S-one startingmaterial mentioned hereinbefore can be prepared as follows:

7.2 g. of 3-bromo-l0,l l-dihydro-5H-dibenzo[a.dlcyclohepten-S-one,together with 2.7 g. of copper cyanide and ml. of dimethylformamide, areheated to boiling under reflux conditions for 6 hours. The resulting hotsolution is poured into a solution containing 10 g. of iron trichloridein ml. of water and 3 ml. of concentrated hydrochloric acid, stirred at70C. for minutes and extracted with toluene. The toluene extract iswashed first with 3N hydrochloric acid and then with 3N caustic soda,dried over sodium sulfate and evaporated. The 3-cyano-10,l l-dihydro-SH-dibenzo[a,d]cyclohepten-5-one which is obtained, is purified byadsorption on the IO-fold amount of Kieselgel (eluting agent: toluene);melting point 104-106C.

EXAMPLE 2 Preparation of 3-chloro-N-(3-methylamino-propyl)-10,1l-dihydro- 5H-dibenzo[a,d]cyclohepten-5-imine oxalate 12.1 g. of3-chloro-l0,l 1-dihydro-5H-dibenzo[a,d- ]cyclohepten-5-one are dissolvedin 700 ml. of absolute benzene at room temperature under an atmosphereof argon with stirring. After the addition of 44 g. ofmethylamino-propylamine, the solution is cooled to 5C. and treateddropwise with a solution of 9 ml. of titanium tetrachloride in 40 ml. ofabsolute benzene. The resulting mixture is stirred at room temperaturefor 48 hours, heated under reflux conditions for 6 hours andsubsequently concentrated to half volume. The concentrate is treatedwith water. The precipitate which forms is removed by filtration andwashed several times with benzene. The aqueous phase is extracted withether. The organic extracts are combined, washed with a saturatedaqueous sodium chloride solution, dried over sodium sulfate andevaporated. The 3-chloro-N- (3-methylamino-propyl)-10,1 l-dihydro-SH-dibenzo[a,d]cyclohepten-5-imine which is obtained is purified byadsorption on a 20-fold amount of neutral aluminum oxide (activity grade11, eluting agent: benzene), dissolved in acetone and treated with asolution of 3.8 g. of oxalic acid in 40 ml. of ethanol. The oxalatewhich precipitates in crystalline form melts at 164167C. afterrecrystallization from acetone/methanol.

The 3-chloro-N-(3-methylamino-propyl)-10,1 1- dihydro5H-dibenzo[a,d]cyclohepten5-imine oxalate is obtained as astereoisomeric mixture in the ratio of about 3:1. The two isomers can beseparated by thin layer chromatography (adsorbent: aluminum oxide MerckF 254, eluting agent: acetone/toluene/diethylamine 49:49:12).

In an analogous manner, utilizing the procedure of Example 2:

from 3-chloro-10,1 1-dihydro-5H-dibenzo[a,dlcyclohepten5-one andethylamino-propylamine, there is obtained 3-chloro-N-(3-ethylaminopropyl)-l0,l l-dihydro-5H-dibenzo[a,d]cyclohepten-S-imine,melting point l69172C. (oxalate); from l-chloro-10,ll-dihydro-5H-dibenzo[a,d]cyclohepten-S-one and methylamino-propylamine,there is obtained l-chloro-N-(3-methylaminopropyl l 0,1l-dihydro5H-dibenzo[a,d]cyclohepten-5-imine, melting point 146149C.(oxalate);

14 from l-chloro-10,l 1-dihydro-5H-dibenzo[a,d ]cyclohepten-S-one andethylamino-propylamine, there is obtained1-chloro-N-(3-ethylaminopropyl)-10,1l-dihydro-5H-dibenzo[a,dlcyclohepten-S-imine, melting point 173C.(oxalate);

from l-methyl-l 0,1 1-dihydro-5H-dibenzo[ a,d ]cy clohepten-S-one andethylamino-propylamine, there is obtained l-methylN-(3-cthylaminopropyl)-10,1 l-dihydro-5H-dibenzo[a,d]cyclohepten-S-imine, melting pointl6ll63C. (oxalate);

from 1 -cyano-10, l 1-dihydro-5H-dibenzo[a,d ]cy clohepten-S-one andethylamino-propylamine, there is obtained1-cyano-N-(3-ethylaminopropyl)- 10,1 1-dihydro-5H-dibenzo[a,dlcyclohepten-S-imine, melting point l29132C. (oxalate);

from 10,1 1-dihydro-5H-dibenzo[a,d]cyclohcpten- 5-one andethylamino-propylamine, there is obtained N-(3-ethylamino-propyl)-10,1l-dihydro- 5H-dibenzo[a,d]cyclohepten-5-imine, melting point 174-176C.(oxalate); and

from 10,1 1-dihydro-5H-dibenzo[a,d lcyclohepten- 5-one andN-methylamino-propylamine, there is obtained N43-methylaminopropyl)-10,1ldihydro-5Hdibenzo[a,d]cyclohepten-5-imine, melting point 198-20lC.(oxalate).

EXAMPLE 3 Preparation of N-( 2-dimethylamino-ethyl )-5H-dibenzo[ a,dlcyclohepten-S-imine oxalate 15.5 g. of 5H-dibenzo[a,d]cyclohepten5-oneare dissolved in 300 ml. of absolute benzene with stirring at roomtemperature and under an atmosphere of argon. Following the addition of66 g. of N,N- dimethylamino-ethylamine, the solution is cooled to 0C.and treated dropwise with a solution of 5.4 ml. of titaniumtetrachloride in 40 m1. of asbolute benzene. The reaction mixture isstirred at room temperature for 48 hours and then filtered. The filtrateis evaporated under reduced pressure. The residue is treated with iceand 3N hydrochloric acid and exhaustively extracted with ether. Theether extract is washed first with water, then with a saturated aqueoussodium chloride solution, dried over sodium sulfate and evaporated, Theresidual N-(Z-dimethylamino-ethyl)-5H-dibenzo[a,dlcyclohepten-S-imine istaken up in acetone and treated with a solution of 2.8 g. of oxalic acidin 40 ml. of ethanol. The oxalate which precipitates in crystalline formmelts at 177179C., after recrystallization from acetone/methanol.

In an analogous manner, utilizing the procedure of Example 3:

from 5H-dibenzo[a,d]cyclohepten-5-one and N.N-dimethylamino-propylamine, there is obtained N- (3-dimethylamino-propyl)5H-dibenzo[ a,d ]cyclohepten-S-imine, melting point l59-161C'.(oxalate);

from 5H-dibenzo[a,d]cyclohepten-5-onc and N,N-diethylaminoethylamine,there is obtained N- (Z-diethylamino-ethyl)-5H-dibenzol a,d]cyclohepten-5imine, melting point 1 l5-l 18C. (oxalate);

from 5H-dibenzo[a,dlcyclohepten-S-one and N,N- diethylaminopropylamine,there is obtained N-(3-diethylamino-propyl)-5H-dibenzo[a,d)cyclohepten-S-imine, melting pointl39l40C. (oxalate);

from lO-bromo-5Hdibenzo[a,d|cyclohepten-5one andN,N-dimethylamino-ethylamine, there is obtained lO-bromo-N-(2-dimethylamino-ethyl )-5H' dibenzola,dlcyclohepten-S-iminc, meltingpoint l73l74C. (oxalate);

from 5H-dibenzo[a,dlcyclohcptemS-one and methylaminopropylamine, thereis obtained N-(3- methylamino-propyl)-5H-dibenzola,d]cyclohepten-S-imine, melting point l5l-l54C (oxalate);

from SH-dibenzol a,d]cycloheptcn-5-one and ethylaminopropylamine, thereis obtained N-(3- ethylamino-propyl )-5H-dibenzo[ a,d ]cyclohepten-5-imine, melting point l5816(lC. (oxalate);

from lO-cyano-5H-dibenzo[a,dlcyclohepten-S-one andN,N'dimethylamino-ethylamine, there is obtainedl()-cyano-l\l-(2-dimethylamino-ethyl)-5H- dibenzo[a,d]cyclohepten5-imine, melting point l87-l89C. (oxalate);

from 3-chloro 5H-dibenzo[a.d]cyclohepten-5-one andN,N-dimethylamino-ethylamine, there is obtained3-chloro-N-(Z-dimethylamino-ethyl)-5H- dibenzolatdlcyclohepten-S-imine,melting point l73l7SC. (oxalate);

from lO-(N,N-dimethyl-sulfonamido)-5H- dibenzo[a,d]cyclohepten-5-one anddimethylamino-ethylamine, there is obtained N-( 2- dimethylamino-ethyl lN,N-dimethylsulfonamido)fiH-dibenzola,d]cycloheptenimine, melting pointl94l96C. (oxalate) and from l-chloro-5H-dibenzo[ a,d ]cyclohepten 5-oneand N,N-dimethylamino-ethylamine, there is obtainedl-chloro-N-(Z-dimethylaminoethyl)-5H- dibenzo[a,d]cyclohepten-5-imine,melting point l66-l69C. (oxalate).

EXAMPLE 4 Preparation of 2-chloro-N( 2-dimethylarnino-ethyl)-thioxanthen-9- imine oxalate 18.6 g. of Z-chloro-thioxanthen-Q-one aredissolved in 350 ml. of absolute toluene with stirring at roomtemperature under an atmosphere of argon. After the addition of 60 g. ofN,N-dimethylamino-ethylamine, the solution is cooled to 0C. and treateddropwise over a period of minutes with a solution of 5 ml. of titaniumtetrachloride in 50 ml. of absolute toluene. The resulting mixture isstirred at room temperature for 76 hours and then filtered. The filtrateis concentrated under reduced pressure. The concentrate is treated withice-water and exhaustively extracted with methylene chloride. Themethylene chloride extract is washed first with water, then with asaturated aqueous sodium chloride solution, dried over sodium sulfateand evapo rated. The 2-chloro-N-(Z-dimethylaminoethyl)thioxanthen9-imine which is obtained is taken up in acetone and treatedwith a solution of 6 g. of oxalic acid in 50 ml. of ethanol. The oxalatewhich precipitates in crystalline form melts at l8ll83C. after drying invacuum.

In an analogous manner, utilizing the procedure of Example 4:

from 2-chloro-thioxanthen-9-one and N,N-

dimethylaminopropylamine. there is obtained 2- chloro N-(3-dimethylaminopropyl )-thioxanthen-9- imine, melting point 176l79C.(oxalate);

from 2-chloro-thioxanthen-Q-one and N,N diethylaminocthylamine, there isobtained 2-chloro- N-( Z-diethylamino-ethyl )-thioxanthen-9 imine,melting point l7ll73C. (oxalate); and from 2'chloro-thioxanthen-9-oneand N,N- diethylaminopropylamine, there is obtained 2- chloro-N-(3-diethylaminopropy] )thioxanthen-9- imine, melting point l44-l46C(oxalate).

EXAMPLE 5 Preparation of N-( 3-dimethylamino-propyl) 10, l ldih vdro-5H-dibenzo[a,d].cyclohepten-5imine oxalate 5.2 g. of lU,ll-dihydro-5H-dibenzola,dlcyclohept en-Sone are dissolved in 200 ml. ofabsolute benzene with stirring at room temperature under an atmosphereof argon. After the addition of 23 g. of N,N- dimethylamino-propylamine,the solution is treated with 4.5 g. of aluminum chloride. The resultingmixture is stirred first at room temperature for 20 hours, then heatedto boiling under reflux conditions for 12 hours and subsequentlyconcentrated and exhaustively extracted with ether. The ether extract iswashed with a saturated aqueous sodium chloride solution, dried oversodium sulfate and evaporated under reduced pressure. N-(3-dimethylamino'propyl l 0,l ldihydro-5H dibenzo{a,dlcycloheptemS-imine,which is obtained, is taken up in acetone and treated with a solution ofl.2 g. of oxalic acid in 20 ml. of ethanol. The oxalate whichprecipitates in crystalline form melts at l50] 52C.

EXAMPLE 6 Preparation of N-( 3-dimethylamino-propyl l 0,1 l-dihydro-SH-dibenzo[a,d lcyclohepten-S-imineoxalate 10.8 g. of10,1l-dihydro-5H-dibenzo[a,d]cyclohepten-5-one are dissolved in 200 ml.of absolute toluene with stirring at room temperature under anatmosphere of argon After the addition of 38 g. of N,N-dimethylamino-propylamine, the solution is cooled to (1C. and treateddropwise with 10 g. of antimony pen tachloride. After the solution warmsto room temperature, the resulting mixture is stirred at C. for 7 hours.Thereafter, the solution is evaporated to half the volume, hydrolyzed byaddition of water and filtered. The filtrate is extracted several timeswith ether. The combined ethereal solutions are washed with 2Nhydrochloric acid. The aqueous phase is made alkaline and extracted withether. The ether extract is washed with a saturated sodium chloridesolution, dried over sodium sulfate and evaporated. The N-(3-dimethylamino-propyl)-10,1 l -dihydro-5 H-dibenzo[a,d]cyclohepten-5-imine which is obtained is dissolved inacetone and treated with a solution of 2.25 g. of oxalic acid in 35 ml.of ethanol. The oxalate which precipitates in crystalline form melts atl52C. after recrystallization from acetone.

EXAMPLE 7 Preparation of N-( 3-dimethylamino-propyl)-10,] l-dihydro-SH-dibenzola,d]cyclohepten-5-imine oxalate 2.6 g. ofl0,ll-dihydro-5H-dibenzo[a,d]cyclohepten-5one are dissolved in I00 ml.of toluene with stirring at room temperature under an atmosphere ofargonv After the addition of 11.5 g. of N,N- dimethylamino-propylamine,the solution is cooled to 0C. and treated slowly with 3.9 g. of antimonytrichloride. After the solution warms to room temperature, the resultingmixture is stirred at 80C. for 6 hours and worked up as described inExample 6. The N(3- dimethylamino-propyl)-10,1 l-dihydro-5H-dibenzo[a,d]cyclohepten-S-imine which is obtained is dissolved inacetone and treated with a solution of 0.9 g. of oxalic acid in 20 ml.of ethanol. The oxalate which precipitates in crystalline form melts at150152C. after recrystallization.

EXAMPLE 8 Preparation of N-(2-dimethylamino-propyl)-10,1 1 -dihydro-5H-dibenzo[a,d )cyclohepten-S-imine oxalate 10.4 g. of 10.11-dihydro-5H-dibenzo[a,d]cyclohepten-5-one are treated with 6.12 g. ofN,N- dimethylamino-propylamine in 20 ml. of absolute tolu ene. After theaddition of 20 g. of a 4A molecular sieve (bead form) the solution isheated under reflux conditions for 20 hours. The molecular sieve is thenremoved by filtration. The filtrate is evaporated. The residue is takenup with ice and 3N hydrochloric acid and extracted with ether. Theaqueous phase is made alkaline and extracted with ether. The combinedether extracts are washed with water and concentrated sodium chloridesolution, dried over sodium sulfate and evaporated under reducedpressure. The N-(2- dimethylaminopropyl)-10,1 l-dihydro-SH-dibenzo[a,d]cyclohepten-5-imine which is obtained is dissolved inacetone and treated with an equivalent amount of oxalic acid in acetone.The oxalate which precipitates in crystalline form melts at 150l 52C.

EXAMPLE 9 Preparation of l-ch1oro-N-(2-methylamino-ethyl)-10,1l-dihydro-SH- dibenzo[a,d]cyclohepten-S-imine oxalate 7.3 g. of1-chloro-10,l l-dihydr-5H-dibenzo[a,d]cyclohepten-S-one and 45 g. ofN-methylethylenediamine are heated overnight to 200C. under anatmosphere of nitrogen in a pressure flask. After evaporation of theexcess amine, the concentrate is treated with ice and 3N hydrochloricacid. The unreacted ketone is extracted with ether. The aqueous phase isthen made alkaline and extracted with ether. The ether extract is washedwith a saturated aqueous sodium chloride solution, dried over sodiumsulfate and evaporated. The 1- chloro-N-(2-methylaminoethyl)-10,1l-dihydro-S H- dibenzo[a,d]cyclohepten-5-imine which is obtained, isdissolved in acetone and treated with an equivalent amount ofhydrochloric acid in ether. The hydrochloride which precipitates incrystalline form melts at 221224C. after recrystallization fromacetone/methano].

In an analogous manner, utilizing the procedure of Example 9:

from 3chloro- 10,1 l-dihydro-5H-dibenzo[a,d ]cyclohepten-S-one andN-methylamino-ethylamine, there is obtained3-chloro-N-(Z-methylaminoethyl 1 0,1 l-dihydro-5H-dibenzo(a,d]cyclohepten-5-imine, melting point 202204C. (hydrochloride);

from 10,1 l-dihydro-S H-dibenzo[a,d ]cyclohepten- S-one andN-methylamino-ethylamine, there is obtained N-( 2-methylaminoethyl 10,11 -dihydro- 18 5H-dibenzo[a,d]cyclohepten-5-imine, point 21 1213C.(hydrochloride);

from 1-chloro-l0,1 1-dihydro-5H-dibenzo[a,d]cyclohepten-S-one andl-dimethylamino-2- propylamine, there is obtained 1-chloro-N-(2dimethylamino-l-methyl-ethyl)-10,l Ldihydro-5H-dibenzo[a,d]cyclohepten-5-imine, melting point 197-200C.(hydrochloride);

from 1-ch|oro-l0,1 1-dihydro-5H-dibenzo[a,d]cyclohepten-S-one andethylenediamine, there is obtained 1-chloro-N(2-aminoethyl) 10,1l-dihydro- 5H-dibenzo[a,d]cyc1ohepten-5-imine, melting point 149l 50C.(maleate from 10,1 l-dihydro-5H-dibenzo[a,d]cyclohepten- 5-one andethylenediamine, there is obtained N-(2- amino-ethyl)- l 0,11-dihydro-5H-dibenzo[a,d]cyclohepten-S-imine, melting point 201202C.(hydrochloride);

from 3-dimethylcarbamoyl-l0,l1-dihydro-5l-ldibenzo[a,d]cyclohepten-5-one and N,N-dimethylamino-ethylamine, there is obtained 3dimethylcarbamoyl-N(2-dimethy1amino-ethyl)- 10,1l-dihydro-5H-dibenzo[a,d ]cyclohepten-S- imine; and

from 3-chlorol 0,1 l-dihydro-5H-dibenzo[a,d]cyclohepten-S-one andethylenediamine. there is obtained 3-chloro-N-(2-aminoethyl)-10,1l-dihydro- 5H-dibenzo[a,d]cyclohepten-5-imine, melting point 226228C.(hydrochloride).

EXAMPLE 10 Preparation of N-(2-pyrro1idino-ethyl)-10,1 l-dihydro-SH-dibenzo[a,d]cyclohepten-5-imine oxalate 20 g. ofN-(2-tosyloxy-ethyl)-10,1 l-dihydro-SH- dibenzo[a,d]cyclohepten-5-imineare dissolved in 180 m1. of toluene and, after the addition of 12.3 ml.of pyrrolidine, heated to boiling under reflux conditions for 15minutes. Subsequently, the resulting mixture is evaporated under reducedpressure. The residue is partitioned between ether and water. The etherphase is separated, washed, dried and evaporated. The oily N-(2-pyrrolidino-ethyl)-10,1 l-dihydro-SH- dibenzola,d]cyclohepten-5-iminewhich is obtained, may be converted into the maleate which has a meltingpoint of l45l46C.

In an analogous manner, utilizing the procedure of Example 10:

from N-( 2-tosyloxy-ethyl)-10,1 l-dihydro-SH-dibenzo[a,d]cyclohepten-S-imine and piperidine, there is obtainedN-(2-piperidino-ethyl)-10,1 1-dihydro-5H-dibenzo[a,d]cyclohepten-S-imine, melting point 14014lC.(maleate);

from N-(2-tosyloxy-ethyl)-10,1 l-dihydro-SH-dibenzo[a,d]cyclohepten-5-imine and dimethylamine, there is obtainedN-(2-dimethylamino-ethyl)- 10,1 1dihydro-5H-dibenzo{a,d ]cyclohepten-S-imine, melting point 13 ll32C. (maleate);

from N-( 2-tosyloXy-ethyl 1 O, 1 1 -dihydro-5H-dibenzo[a,d]cyclohepten-S-imine and diethylamine, there is obtainedN-(2-diethylamino-ethyl)- 10,11-dihydro-5H-dibenzo[a.d]cycloheptenfiimine, melting point 126C.(oxalate); and

from N-(2-tosyloxy-ethyl)-10,1 l-dihydro-S H-dibenzola,d]cyclohepten-5-imine and hydroxypropyl-piperazine, there isobtained N-[2- (4-hydroxypropylpiperazino)-ethyl 10. l lmelting 19dihydro-SH-dibenzo[a,d]cyc1ohepten-5-imine, melting point 136-l40C.(dimaleate).

The N-(2-tosyloxy-ethyl)-10,1 l-dihydro-SH-dibenzo[a,d]cyclohepten-5-imine employed as the starting material can beprepared as follows:

600 ml. of ethanolamine are added to 208 g. of 10,1-l-dihydro-5H-dibenzo[a,d lcyclohepten-S-one. The mixture is heated underreflux conditions in an inert gas atmosphere for 16 hours. The refluxingethanolamine is recycled into the reaction vessel through a Soxhletattachment filled with 2 X 130 g. of 4A molecular sieve (bead form, 2mm.', Merck). The resulting mixture is then evaporated. The residue isdissolved in ether. The ether solution is washed with water andextracted with ice-cold 1N nitric acid. The acid extracts are washedwith ether, adjusted to a pH value of l12 by addition of coldconcentrated sodium hydroxide solution and subsequently extracted withmethylene chloride. The methylene chloride extract is washed with water,dried over calcium chloride and evaporated under reduced pressure. TheN-(2-hydroxy-ethyl)-10,l l-dihydro-5H dibenzo[a,d]cyclohepten-5-iminewhich is obtained melts at 9394C. after recrystallization fromacetone/petroleum ether: 3:5.

A solution of 150 g. of N (2-hydroxy-ethyl)-l0,lldihydro-5H-dibenzo[a,d]cyclohepten-5imine in 1000 ml. of absolutebenzene and 165 ml. of triethylamine is treated dropwise at 5l0C. over aperiod of 30 minutes with a solution of 119.5 g. of p-toluenesulfonylchloride in 500 ml. of absolute benzene. The resulting mixture isstirred at room temperature for 48 hours, then poured onto ice-water.The benzene phase is separated, washed, dried and evaporated. The N-(2-tosyloxyethyl)- 10,1 l -dihydro-5H-dibenzo[ a,d lcyclohepten-S-iminewhich is obtained melts 1 14l 16C. after recrystallization from ethanol.

The following Examples illustrate several pharmaceutical formulationscontaining the tricyclic imines of the invention:

EXAMPLE 1 l Tablets of the following composition are prepared:

3-chlnrti N( 2dimethylamino-ethyl 10,] I I0 mg.

dihydro-SH-dibenzoladlcyclohepwn-iiilim lactose 63 mg.

corn starch 74 mg.

talcum 2.7 mg.

magnesium stearate 0.3 m 150 mg.

The active ingredient is mixed with the lactose and the corn starch andgranulated with the aid of ethanol. The granulate is dried and, afterthe addition of talcum, compressed into tablets.

EXAMPLE 12 Capsules of the following composition are prepared:

N-(2dimethylamino-ethyl)-5H-dibenzo[a dlcy- 25 mg.

clohepten-S-imine lactose 150 mg.

corn starch 30 mg.

talcum 5 The active ingredient is homogeneously mixed with theadjuvants, passed through a sieve (mesh-width 0.23 mm.) and filled withgelatin capsules.

EXAMPLE 13 Dragees of the following composition are prepared:

1-chloro-N(2dimethylamino-ethyl 10,l l- 25 mg.

dihydro-5H-diben7o|a,dIcyclohepten-S-imine mannitol mg.

corn starch 20 mg.

talcum 5 mg. mg.

The active ingredient is passed through a sieve (mesh-width 0.23 mm.)with the mannitol. A 10 percent aqueous paste is prepared from the cornstarch and homogeneously mixed with the mannitol/active ingredientmixture. The moist mass is passed through a sieve (mesh-width 1.0 mm.).The granulate obtained is dried and, after the addition of talcum,compressed to cores which are coated with a sugar layer in conven tionalmanner by dredging.

EXAMPLE 14 Tablets of the following composition are prepared:

l-bromo-N-( 2-dimethylaminoethyl l 0,1 1- 10 mg.

dihydro-SH-dibenzoi a,d lcyclohepten-S-imine silicic acid 25 mg.

lactose ll5 mg.

com starch 50 mg.

calcium stearate 10 mg. 210 mg.

The active ingredient is well mixed with the other adjuvants, granulatedand compressed into tablets.

We claim:

1. A compound of the formula

1. A COMPOUND OF THE FORMULA
 2. A compound of the formula,N-(2-tosyloxyethyl)-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5-imine.